Cerebral Blood Flow and Amyloid-β Interact to Affect Memory Performance in Cognitively Normal Older Adults.

Katherine J Bangen,Emily C Edmonds,Mark W Bondi,Daniel A Nation,Lyzette E Locano,My Tran,Zvinka Z Zlatar,Alexandra L Clark,Kelsey R Thomas,Nicole D Evangelista,Lisa Delano-Wood,Madeleine L Werhane

doi:10.3389/fnagi.2017.00181

Abstract

Cerebral blood flow (CBF) alterations and amyloid-β (Aβ) accumulation have been independently linked to cognitive deficits in older adults at risk for dementia. Less is known about how CBF and Aβ may interact to affect cognition in cognitively normal older adults. Therefore, we examined potential statistical interactions between CBF and Aβ status in regions typically affected in Alzheimer’s disease (AD) within a sample of older adults from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. Sixty-two cognitively normal participants (mean age = 72 years) underwent neuroimaging and memory testing. Arterial spin labeling magnetic resonance imaging was used to quantify CBF and florbetapir PET amyloid imaging was used to measure Aβ deposition. Aβ status (i.e., positivity versus negativity) was determined based on established cutoffs (Landau et al., 2013). The Rey Auditory Verbal Learning Test was used to assess memory. Linear regression models adjusted for age, education, and sex, demonstrated significant interactions between CBF and Aβ status on memory performance. Among Aβ positive older adults, there were significant negative associations between higher CBF in hippocampus, posterior cingulate, and precuneus and poorer memory performance. In contrast, among Aβ negative older adults, there were no significant associations between CBF and cognition. Our findings extend previous CBF studies of dementia risk by reporting interactions between Aβ status and CBF on memory performance in a sample of well-characterized, cognitively normal older adults. Results suggest that differential CBF-cognition associations can be identified in healthy, asymptomatic Aβ positive older adults relative to Aβ negative individuals. Associations between higherCBF and poorer memory among Aβ positive older adults may reflect a cellular and/or vascular compensatory response to pathologic processes whereby higher CBF is needed to maintain normal memory abilities. Findings indicate that CBF and its associations with cognition may have utility as a reliable marker of brain function early in the AD process when interventions are likely to be beneficial.

Highlights

Cerebral blood flow (CBF) alterations (Bangen et al, 2014) and amyloid-β (Aβ) accumulation (Rodrigue et al, 2012) have been independently linked to increased risk of developing dementia
A series of multiple hierarchical linear regression models adjusting for age, education, and sex were first performed to determine whether there was an interaction between Aβ status and CBF of the regions of interest (ROIs) on the post-interference recall score
A second set of multiple linear regressions were performed to determine whether there was an interaction between Aβ status and CBF of our ROIs for recognition memory performance

Summary

INTRODUCTION

Cerebral blood flow (CBF) alterations (Bangen et al, 2014) and amyloid-β (Aβ) accumulation (Rodrigue et al, 2012) have been independently linked to increased risk of developing dementia. ASL techniques have advantages over PET and SPECT including (1) non-invasive use of an endogenous tracer rather than an intravenously administered contrast agent; (2) relatively brief scan times (typically 5–10 min) and can be repeated in short succession due to the magnetization of the labeled blood water that decays within seconds; and (3) quantitative measurement of CBF at rest or during a functional task (Johnson et al, 2005) These advantages along with its increased sensitivity and ability to quantitatively measure perfusion make it ideal to extend its applications for research and in clinical settings (Telischak et al, 2015) designed to monitor neural and vascular changes in healthy aging and disease. We examined potential statistical interactions of ASL MRI CBF and Aβ status on cognitive function within a sample of normally aging older adults drawn from the ADNI study

MATERIALS AND METHODS

Participants

RESULTS

DISCUSSION